Psammaplins Selectively Target Triple-Negative Metastatic Breast Tumor Cells that are Genetically Programmed to Colonize Specific Organs

Five bromotyrosine-derived marine sponge metabolites, four psammaplins (1 – 4) and the psammaplin dimer, bisaprasin (5) were isolated from a lipid extract sample of the marine sponge Dendrilla lacunosa.  Psammaplins act as histone deacetylase (HDAC) inhibitors that alter cellular gene expression.  The D. lacunosa psammaplins activated the oxygen regulated transcription factor HIF-1 (hypoxia-inducible factor-1) in T47D human breast tumor cells and displayed cell line specific effects against aggressive organotropic metastatic cell lines that were derived from triple-negative MDA-MB-231 human breast tumor cells

CONTRIBUTION OF INTERLEUKIN 6 TRANS SIGNALING IN PULMONARY FIBROSIS

Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis and showed that protease-mediated cleavage was important in production of sL-6Rα in fibrotic lungs. In vivo neutralization of sIL-6Rα, and resulting antagonism of IL-6 trans signaling, attenuated pulmonary fibrosis in mice. Decreases in sIL-6Rα were associated with reductions in myofibroblasts, fibronectin and collagen. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. These findings suggest that IL-6 trans signaling influences events crucial in pulmonary fibrosis in vivo

A Carleman-Picard approach for reconstructing zero-order coefficients in parabolic equations with limited data

We propose a globally convergent computational technique for the nonlinear inverse problem of reconstructing the zero-order coefficient in a parabolic equation using partial boundary data. This technique is called the "reduced dimensional method". Initially, we use the polynomial-exponential basis to approximate the inverse problem as a system of 1D nonlinear equations. We then employ a Picard iteration based on the quasi-reversibility method and a Carleman weight function. We will rigorously prove that the sequence derived from this iteration converges to the accurate solution for that 1D system without requesting a good initial guess of the true solution. The key tool for the proof is a Carleman estimate. We will also show some numerical examples